Recently, it has become more and more apparent that dendritic cells (DC) play an important role as an interface between an environmental factor and an immune response. Dendritic cells are cells differentiated from monocytes of hematopoietic stem cell origin, and known as major antigen-presenting cells (APCs) together with macrophages and B cells. Only dendritic cells do function as professional APCs capable of inducing a primary response of naive T cells by presenting an antigen to the naive T cells. Particularly, antigen presentation by dendritic cells is essential to induce differentiation into helper T cells (Th cells). In the antigen presentation by dendritic cells, a protein antigen incorporated by phagocytosis is fragmented into peptides, and the peptides (antigenic peptides) are bound to MHC class I molecules or MHC class II molecules and thus transported to the surfaces of the dendritic cells.
Meanwhile, there is known an active substance other than a protein antigen involved in antigen presentation as described above. Unlike a protein antigen, the active substance increases the antigen-presenting function of dendritic cells irrespectively of the type of antigen and enhances an immune response. Such a substance is called an adjuvant. A portion of an adjuvant binds to a specific, TOLL-like receptor (TLR) on the surface of an immature dendritic cell (immature DC: iDC). The signal is transmitted into the cell, and thereby the immature dendritic cell is activated and differentiated into a mature dendritic cell (mature DC: mDC) (see, for example, NPL 1). Several types of mature dendritic cell are known, which respectively have different differentiation-inducing activities on naive CD4-positive T cells. Generally, a mature dendritic cell inducing a Th1 (T helper 1) cell is called DC1; a mature dendritic cell inducing a Th2 (T helper 2) cell is called DC2; a mature dendritic cell inducing a Th17 (T helper 17) cell is called DC17; and a mature dendritic cell inducing a Tr (T regulatory) cell is called DCr. Moreover, an adjuvant having an activity of differentiating an immature dendritic cell into DC1 is called a Th1 adjuvant; an adjuvant having an activity of differentiating an immature dendritic cell into DC2 is called a Th2 adjuvant; an adjuvant having an activity of differentiating an immature dendritic cell into DC17 is called a Th17 adjuvant; and an adjuvant having an activity of differentiating an immature dendritic cell into DCr is called a Tr adjuvant.
A lipopolysaccharide (LPS) principally produced by a bacterium, and the like are known as the Th1 adjuvant; phosphatidylserine that is a phospholipid derived from a schistosome, and the like are known as the Th2 adjuvant; curdlan and the like are known as the Th17 adjuvant; and lysophosphatidylserine and the like are known as the Tr adjuvant (see, for example, NPL 2).
It is known that many immune diseases occur when the equilibrium state of the function of Th cells is disturbed (Th imbalance). For example, autoimmune diseases such as type 1 diabetes are known as diseases caused by excessive activation of Th1 cells, and allergic diseases such as atopic dermatitis and asthma are known as diseases caused by excessive activation of Th2 cells. Thus, into which Th cell an adjuvant has an activity of inducing the differentiation of a naive CD4-positive T cell is important in immune response reactions and also in treatment of immune diseases.
Among specified substances such as environmental substances and chemical substances surrounding our lives, there are many substances having an activity of modifying an immune response as an adjuvant. Indeed, some of these specified substances are known as causative factors of allergic diseases such as atopicdermatitis, pollen allergy, and bronchial asthma, threatening human healthy lives at present. Thus, evaluating the adjuvant activity of a specified substance, particularly evaluating on which Th cell a specified substance has the adjuvant activity, is important in predicting the influence of specified substances on a human body. Moreover, it is also quite important in checking the safety of manufactured products and the like including specified substances, and checking the efficacy of drugs and the like including specified substances.
For this reason, the present inventors have developed a method for evaluating an adjuvant activity on Th cells using dendritic cells (Patent Literature 1). Further, an association has been found out between atopic dermatitis and a Th2 adjuvant activity in mother's milk as a result of detecting the Th2 adjuvant activity in mother's milk taken by infants who developed atopic dermatitis using THP-1 cells as dendritic cells (NPL 3).
However, an entity of the Th2 adjuvant activity in mother's milk has not been revealed yet.